Effects of Enteral Feeding Regimens on NEC, Mortality, and Neurodevelopment in Very Preterm Infants

NCT ID: NCT07045844

Last Updated: 2025-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

2324 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-01

Study Completion Date

2030-07-31

Brief Summary

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The goal of this clinical trial is to evaluate whether supplementing with pasteurized donor human milk (pHDM) or preterm formula (PTF) when own mother's milk (OMM) is insufficient can improve outcomes in very preterm infants born before 29 weeks of gestation. It also aims to assess whether routine use of human milk fortifiers benefits this population. The main questions it aims to answer are:

Does supplementing OMM with pHDM or PTF improve survival without surgery-requiring necrotizing enterocolitis (NEC) by 34 weeks corrected gestational age? Is routine fortification of human milk better than selective fortification based on growth faltering?

Researchers will compare:

pHDM vs. PTF to see which better supports survival without severe NEC. Routine fortification vs. selective fortification to assess the impact on growth and long-term neurodevelopment.

Participants will:

Be randomized twice:

* First, within the first week of life to receive either pHDM or PTF when OMM is insufficient
* Second, in the second week of life to receive either routine fortification or selective fortification only if growth faltering occurs Receive feeding and care as per standard clinical practice Complete neurodevelopmental assessment at 2 years corrected age using the PARCA-R tool (no additional study visits required) This multicenter, double-randomized, open-label randomized controlled trial is embedded in routine neonatal care and uses real-world data to assess both short- and long-term outcomes.

Detailed Description

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Conditions

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Very Preterm Infant Necrotizing Enterocolitis (NEC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Pasteurized Donor Milk for Insufficient Breastfeeding

Participants receive pasteurized donor human milk (pHDM) as supplemental feeding when the clinician determines maternal milk supply is insufficient.

Group Type EXPERIMENTAL

Pasteurized Donor Milk for Insufficient Breastfeeding

Intervention Type DIETARY_SUPPLEMENT

Participants receive pasteurized donor human milk (pHDM) as supplemental feeding when the clinician determines maternal milk supply is insufficient.

Randomization 1 will occur when the clinician determines that supplemental feeding is required due to insufficient breast milk supply.

Routine fortification

Intervention Type DIETARY_SUPPLEMENT

Randomization 2 will be conducted when the total daily intake of human milk (including own mother's milk \[OMM\] and/or donor pasteurized human milk \[pHDM\] ) reaches between 60-120 mL/kg

Rescue fortification

Intervention Type DIETARY_SUPPLEMENT

Randomization 2 will be conducted: Add fortifiers when the infant meets predefined criteria for growth faltering (Preterm infants exhibit a sustained decline in growth velocity for weight, length, or head circumference, demonstrated by a downward crossing of centiles on growth curves, despite tolerating and consuming at least 180 mL/kg/day of breast milk or formula. Blood urea levels in these infants remain consistently below 1.5 mmol/L, and there are no severe complications such as active sepsis or the need for vasoactive medications to maintain circulatory stability. Chronic sodium depletion has also been ruled out, as this condition alone can lead to growth failure. Additionally, preterm infants are unable to tolerate high-volume feeding of 180 mL/kg/day due to specific reasons, such as severe gastroesophageal reflux or the presence of a high-output stoma following surgical procedures).

Preterm formula for Insufficient Breastfeeding

Participants receive preterm formula (PTF) as supplemental feeding when the clinician determines maternal milk supply is insufficient.

Group Type EXPERIMENTAL

Preterm Formula for Insufficient Breastfeeding

Intervention Type DIETARY_SUPPLEMENT

Participants receive preterm formula (PTF) as supplemental feeding when the clinician determines maternal milk supply is insufficient.

Randomization 1 will occur when the clinician determines that supplemental feeding is required due to insufficient breast milk supply.

Routine fortification

Intervention Type DIETARY_SUPPLEMENT

Randomization 2 will be conducted when the total daily intake of human milk (including own mother's milk \[OMM\] and/or donor pasteurized human milk \[pHDM\] ) reaches between 60-120 mL/kg

Rescue fortification

Intervention Type DIETARY_SUPPLEMENT

Randomization 2 will be conducted: Add fortifiers when the infant meets predefined criteria for growth faltering (Preterm infants exhibit a sustained decline in growth velocity for weight, length, or head circumference, demonstrated by a downward crossing of centiles on growth curves, despite tolerating and consuming at least 180 mL/kg/day of breast milk or formula. Blood urea levels in these infants remain consistently below 1.5 mmol/L, and there are no severe complications such as active sepsis or the need for vasoactive medications to maintain circulatory stability. Chronic sodium depletion has also been ruled out, as this condition alone can lead to growth failure. Additionally, preterm infants are unable to tolerate high-volume feeding of 180 mL/kg/day due to specific reasons, such as severe gastroesophageal reflux or the presence of a high-output stoma following surgical procedures).

Interventions

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Pasteurized Donor Milk for Insufficient Breastfeeding

Participants receive pasteurized donor human milk (pHDM) as supplemental feeding when the clinician determines maternal milk supply is insufficient.

Randomization 1 will occur when the clinician determines that supplemental feeding is required due to insufficient breast milk supply.

Intervention Type DIETARY_SUPPLEMENT

Preterm Formula for Insufficient Breastfeeding

Participants receive preterm formula (PTF) as supplemental feeding when the clinician determines maternal milk supply is insufficient.

Randomization 1 will occur when the clinician determines that supplemental feeding is required due to insufficient breast milk supply.

Intervention Type DIETARY_SUPPLEMENT

Routine fortification

Randomization 2 will be conducted when the total daily intake of human milk (including own mother's milk \[OMM\] and/or donor pasteurized human milk \[pHDM\] ) reaches between 60-120 mL/kg

Intervention Type DIETARY_SUPPLEMENT

Rescue fortification

Randomization 2 will be conducted: Add fortifiers when the infant meets predefined criteria for growth faltering (Preterm infants exhibit a sustained decline in growth velocity for weight, length, or head circumference, demonstrated by a downward crossing of centiles on growth curves, despite tolerating and consuming at least 180 mL/kg/day of breast milk or formula. Blood urea levels in these infants remain consistently below 1.5 mmol/L, and there are no severe complications such as active sepsis or the need for vasoactive medications to maintain circulatory stability. Chronic sodium depletion has also been ruled out, as this condition alone can lead to growth failure. Additionally, preterm infants are unable to tolerate high-volume feeding of 180 mL/kg/day due to specific reasons, such as severe gastroesophageal reflux or the presence of a high-output stoma following surgical procedures).

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Gestational age at birth less than 29 weeks;
* No contraindications to enteral feeding;
* Mother is willing to breastfeed.

Exclusion Criteria

* For Randomization Group 1: If the infant has already received pasteurized human donor milk (pHDM), preterm formula (PTF), or nutritional fortifiers;
* For Randomization Group 2: If the infant is exclusively fed with preterm formula and the mother has no intention to express breast milk;
Minimum Eligible Age

1 Day

Maximum Eligible Age

14 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Imperial College London

OTHER

Sponsor Role collaborator

The Children's Hospital of Zhejiang University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Yanping Xu

Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Yongkang Maternity and Child Health Care Hospital

Guli, Zhejiang, China

Site Status

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Women's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Hangzhou Women's Hospital

Hangzhou, Zhejiang, China

Site Status

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Jiaxing Maternity and Child Health Care Hospital

Jiaxing, Zhejiang, China

Site Status

Ningbo Women and Children's Hospital (The Affiliated Women and Children's Hospital of Ningbo University)

Ningbo, Zhejiang, China

Site Status

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status

Yiwu Maternity and Child Health Care Hospital (Yiwu Branch of The Children's Hospital, Zhejiang University School of Medicine)

Yiwu, Zhejiang, China

Site Status

Countries

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China

Central Contacts

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Yanping Xu

Role: CONTACT

8613685757726

Facility Contacts

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Aijuan Yang

Role: primary

8613506790182

Zheng Chen

Role: primary

0571-13857151000

Fang Luo

Role: primary

8613616542920

Jiajun Zhu

Role: primary

8613858089111

Weinong Mo

Role: primary

8613606719109

Zhou Jiang

Role: primary

8613588878072

Huafei Huang

Role: primary

8613867344127

Qin Lv

Role: primary

8613738822179

Shangqin Chen

Role: primary

8613819735725

Keran Ling

Role: primary

8618314930492

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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2025-IRB-0232-P-02

Identifier Type: -

Identifier Source: org_study_id

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